Velocity-selective arterial spin labeling without spatial selectivity

ABSTRACT

Techniques for providing velocity-selective magnetic arterial spin labeling in magnetic resonance imaging (MRI) without spatial selectivity. In one implementation, an RF pulse train is applied to selectively tag spins according to velocities of the spins without selection based on locations of the spins. MRI images of tagged spins at an area of interest are then acquired to obtain information on perfusion at the area of interest.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national stage application of and claims thebenefit of PCT Application No. PCT/US03/14978, filed on May 13, 2003,and published as WO 03/094728, which claims the benefit of U.S.Provisional Application No. 60/378,154 entitled “Perfusion Imaging UsingMRI” and filed May 13, 2002, the disclosure of which is incorporatedherein by reference as part of this application.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The invention was made with government support under Grant Nos. NS36211and NS36722 awarded by the National Institutes of Health (NIH). Thegovernment has certain rights in the invention.

BACKGROUND

This application relates to arterial spin labeling (ASL) in magneticresonance imaging (MRI).

Imaging through MRI techniques is well known. In essence, a typical MRItechnique produces an image of a selected body part of an object underexamination by manipulating the magnetic spins of hydrogen atoms in thebody part such as fat and water molecules and processing measuredresponses from the magnetic spins. A MRI system may include hardware togenerate different magnetic fields for imaging, including a staticmagnetic field along a z-direction to polarize the magnetic spins,gradient fields along mutually orthogonal x, y, or z directions in a xyzcoordinate system to spatially select a body part for imaging, and an RFmagnetic field (B₁) to manipulate the spins. MRI techniques may be usedto capture the functional changes in body parts or tissues such as thebrain perfusion.

One commonly-used technique for functional MRI is in vivo imaging byarterial spin labeling (ASL), where the arterial blood is tagged bymagnetic inversion using RF pulses applied to a plane or slab ofarterial blood proximal to the tissue of interest. Images are typicallyacquired with and without prior tagging of arterial blood and aresubtracted to produce images that are proportional to perfusion. Thismagnetic tagging allows for the imaging of blood flow without theadministration of dyes or other imaging agents. Hence, ASL providesnon-invasive tagging in MRI measurements.

Methods based on such ASL, however, are spatially selective and thusrequire the tagging be done at a plane or slab close to the targetissues. Notably, there is a transit delay (Δt) for the delivery oftagged blood to the target tissues. This delay can be on the order ofthe T1 time of blood and is probably the largest source of errors in thequantitation of cerebral blood flow using ASL in the human brain. Morespecifically, the time for delivery of the tagged blood to the targettissues by blood flow is not short compared to the lifetime of thetracer (T1). The T1 of blood is approximately 1.3 seconds, while thedelivery time in the brain is about 0 to 2 seconds in healthy subjectsand may reach 5 to 10 seconds in pathological cases. Such heterogeneityof delivery time usually arises from variations in the distances andflow velocities along the vascular tree from the tagging location to thetissues of interest. In the important clinical applications such asstroke, the collateral routes of blood circulation can lead to adelivery time much larger than the time T1 and thus can cause falsepositive findings of low perfusion when in fact perfusion is present viacollateral routes of circulation.

Such spatial selectivity and the associated delay are undesirable andare present in various available ASL methods including EPISTAR, PICORE,FAIR, QUIPPS and continuous ASL techniques. In pulsed techniques, a slabof tissue containing arterial blood is tagged, while in the continuoustechniques blood flowing through a defined plane is tagged upontraversal of the plane. Pulsed and continuous techniques based onspatially dependent tagging are generally susceptible to delivery timerelated artifacts.

SUMMARY

In recognition of the above, this application discloses velocityselective ASL (VS-ASL) in which the tag pulse is velocity selectiveinstead of spatially selective to mitigate adverse effects in connectionwith the delay in the delivery of tagged blood from the site of taggingto the tissue of interest. This allows for the tagging of all flowingspins, regardless of their physical location. Because the tag is notspatially selective, multislice and 3D acquisitions are limited only byimaging speed, and not by transit parameters.

In one implementation of VS-ASL, an RF pulse train is applied toselectively tag spins according to velocities of the spins withoutselection based on locations of the spins. MRI images of tagged spins atan area of interest are then acquired to obtain information on perfusionat the area of interest. RF pulse trains such as(α_(i)−grad_(i)−180−grad_(i))_(n)−α_(n+1) and hyperecho-based trains maybe used.

In another implementation, a velocity-selective tagging RF pulse isapplied to selectively tag spins according to velocities of arterialspins flowing to an area of interest without selection based onlocations of the arterial spins. A first MRI image of tagged arterialspins at the area of interest is subsequently obtained. This can be usedto improve the quantification of tissue perfusion using VS-ASL. A secondMRI image of the same area of interest is also obtained without thevelocity-selective tagging RF pulse. Next, a difference between thefirst and the second MRI images is used to obtain information onperfusion at the area of interest.

These and other implementations are described with greater details inthe drawings, the detailed description, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B illustrate two exemplary implementations of velocityselective arterial spin labeling without spatial selectivity.

FIGS. 2A and 2B illustrate one exemplary RF pulse train suitable for thevelocity selective ASL of this application.

FIGS. 3A, 3B, and 3C show exemplary MRI images obtained using the RFpulse train in FIG. 2A.

FIG. 4 shows one exemplary hyperecho pulse train for implementing theVS-ASL technique of this application.

FIG. 5 shows the velocity profile for the hyperecho pulse train in FIG.4 in comparison with that for the spin echo pulse train shown in FIG.2A.

FIG. 6 shows an exemplary acquired VS-ASL image at 3 T using thehyperecho pulse train in FIG. 4.

DETAILED DESCRIPTION

The VS-ASL techniques for MRI measurements in this application may beused much more effectively than the spatially selective ASL techniquesin a variety of clinical applications including acute stroke. Ingeneral, the present techniques tag arterial blood with velocityselective, rather than spatially selective, RF pulses. As a result,nearly all arterial blood can be tagged irrespective of location. Thisnon-spatial selection in tagging brings the tag much closer to thetarget tissues for the entire brain. In comparison, the conventional ASLtechniques are known to fail in the presence of long delivery times andare difficult to improve over many slices. By contrast, in thenon-spatially-selective VS-ASL techniques of this application, thedelivery delay should be small everywhere, and the technique isexplicitly independent of the location of the imaging slices.

In preferred implementations, velocity selective tagging may beaccomplished using an RF/gradient pulse train that saturates or invertsmagnetization of the spins in the flow traveling above a cut-offvelocity V_(c), without perturbing the spins that are moving slower thanV_(c). Typically, the cut-off velocity V_(c) may be set on the order of1 cm/s in some applications.

A typical VS-ASL RF pulse sequence may be applied as follows. First, avelocity-selective tagging RF pulse is applied to modify themagnetization of inflowing arterial spins. Second, a delay of a durationof the T_(I) time (i.e., a time on the order of the T₁ of blood, whichis approximately 1-2 seconds) is permitted to allow for inflow to reachthe target issues. Upon expiration of the delay, a rapid imageacquisition is performed to acquire an image of a region of interest.This is alternated across the repetition time TR periods with images inwhich flowing spins have not been tagged. The two images are subtractedto obtain an image that reflects only the blood that has flowed in theregion of interest.

FIGS. 1A and 1B respectively illustrate two techniques for improving thequantitation of perfusion using velocity selective ASL without thespatial selectivity. FIG. 1A illustrates the first technique usingpulsed ASL. During one cycle within the imaging repetition time TR,three pulse trains are applied to the target area for the MRI imaging.Initially, a VS-ASL RF pulse train 110 is applied to tag spins with avelocity selectivity without selection based on spin locations. After atime TI₁ which is less than the time TI, a second VS-ASL RF pulse train120 is applied to destroy the signal from spins that are still movingfaster than the cutoff velocity V_(c). After the second VS-ASL pulsetrain 120 within a time less than TI from the application of the firstVS-ASL pulse train 110, a third pulse train 130 for a fast imageacquisition is applied to acquire the image of the target area. Thiscompletes one imaging cycle to get a velocity selective MRI image of thetarget. In the next imaging cycle, a MRI image is acquired with the fastimage acquisition without the tagging pulse train 110 and the velocityselective pulse train 120. The difference between the two imagesprovides the information of the perfusion in the target area.

Application of the second VS-ASL pulse train 120 limits the signal onlyto those spins that decelerated from a velocity higher than V_(c) to avelocity lower than V_(c) in the time TI₁, and performs two functions.First, it restricts the temporal length of the tagged bolus to TI₁. Thisin turn generates an ASL signal that is proportional to the product ofperfusion and TI₁, and makes it possible to quantify the absolute levelof perfusion. Second, it eliminates the signal from veins, as blood inveins is accelerating rather than decelerating. This modification hasbeen implemented in the form of a second identical velocity selectivepulse at time TI₁ after the application of the tag pulse. The ASL signalproduce by this technique is proportional to CBF*TI₁.

FIG. 1B shows the second technique using pulsed ASL to image only spinswith velocities below V_(c). Different from the first technique in FIG.1A, only two pulse trains are applied in each imaging cycle. The firsttagging pulse train 110 is similar to that in FIG. 1A. Instead ofapplying the pulse trains 120 and 130 within the time TI, a pulse train140 is applied within a time less than TI to perform a velocityselective fast image acquisition. Hence, different from the pulse train130 which performs only the fast image acquisition, the pulse train 140is designed to perform a fast image acquisition with a velocityselectivity to select only tagged spins with a velocity below the cutoffVc to image. This VS fast image acquisition pulse may be implementedwith a suitable VS pulse train, such as a bipolar velocity sensitivegradient pulses (90-degree pulse followed with two bipolar gradientpulses with opposite phases) or other set of velocity sensitive gradientpulses during image acquisition. This approach, when combined with asingle shot imaging technique, has the advantage of being insensitive tothe phase shifts that arise from gross patient motion during applicationof velocity sensitive preparation pulses.

Various velocity-selective RF pulse trains may be used to implement theabove VS-ASL techniques. Computer optimization techniques may be used todevelop or identify RF pulse trains with desired velocity selectivityover a wide range of velocities.

For example, a 90_(x)−grad−180_(y)−grad−90_(−x) pulse train was testedto exhibit an approximately sinc-shaped magnetization profile (M_(z)) asa function of velocity in the presence of laminar flow. A VENC (velocitydecoding speed) of approximately 1-cm/s tags spins down to the level ofapproximately 50-μm vessels, which should be close to the target tissue.The control pulse is the same train with the gradients turned off. FIG.2A shows two sequential pulse trains with and without the RF tagginggradient pulses for taking the images. FIG. 2B shows the velocityselectivity caused by the VS-ASL with the90_(x)−grad−180_(y)−grad−90_(−x) pulse train in FIG. 2A.

In order to quantify cerebral blood flow (CBF), it is desirable tocontrol or measure the temporal width of the bolus of tagged blood thatis being delivered to the tissue. One method for the quantification ofCBF is to introduce the velocity selectivity into the image acquisitionusing flow weighting gradients. If the flow weighting gradients in theimaging sequence have the same velocity cutoff (V_(c)) as the tag pulse,and the tagged arterial blood is decelerating monotonically, then onlyblood that decelerates through this cutoff velocity V_(c) during TI willcontribute to the ASL signal, and the ASL signal will be proportional toCBF*TI. The condition for this approach is that the velocity cutoffV_(c) is sufficiently small that the deceleration through that velocityV_(c) occurs within the imaging voxel. This technique is referred hereinas quantitative VS-ASL (QVS-ASL). Imaging techniques for acquiring MRIimages without a velocity selective readout are labeled non-quantitativeASL (NQVS-ASL).

FIGS. 3A, 3B, and 3C illustrate MRI images obtained from healthyvolunteers by using a 1.5T GE LX MRI system. A single shot spiralreadout at 64×64 resolution, with a field of view (FOV) about 24 cm by 8mm. Multislice images were acquired sequentially from proximal todistal, with a delay of approximately 60 ms between images. FIG. 3Ashows the multislice VS-ASL images where the top images are NQVS-ASLimages and the bottom images are QVS-ASL images with TI from about 600ms to about 900 ms. FIG. 3B shows VS-ASL images at different TI times of700 ms, 800 ms, 1100 ms, and 1300 ms from left to right. The top rowshows the NQVS-ASL images and the bottom row shows the QVS-ASL images.FIG. 3C further shows PICORE QUIPSS II and three QVS-ASL images at TI ofabout 1100 ms and VENC at 0.5, 1.0. and 2.0 cm/s, respectively.

Other exemplary pulse trains suitable for VS-ASL of this applicationinclude pulse trains of (α_(i)−grad_(i)−180−grad_(i))_(n)−α_(n+1), andhyperecho-based trains. When α_(i) is set at 90 degrees, the pulse trainof (α_(i)−grad_(i)−180−grad_(i))_(n)−α_(n+1) is a spin echo pulse train.In general, α_(i) may be set to other angles. Based on Bloch equationsimulations, it appears that the hyperecho based trains are more timeefficient. This is presumably because the off-resonance insensitivity isprovided by a single 180° pulse at the center of the train in thehyperecho trains, as opposed to multiple 180° pulses.

In particular, velocity selective hyperecho pulse trains of the form of(α_(i)−grad_(i))_(n)−180−(−α_(n+1−i)−grad_(n+1−i))_(n) may be designedusing the Nelder-Mead simplex method to optimize the αi, their phases,and the area of the gradients. The error function is the mean squareddifference between the velocity profile and an ideal rectangular profilewith a velocity cutoff at V_(c)=1 cm/s. For B1 insensitivity, BIR-4pulses described in Journal of Magnetic Resonance, Vol. 94, page 511(1991) by Garwood et al. with tan(κ)=3, ζ=3 and a width of 6 ms wereused for all pulses. This class of RF pulses provides for accurate planerotation of all spins over a broad range of B₁ field intensities. Foroptimizations, T1 and T2 were assumed to be 1000 ms and 100 ms,respectively, and pulse trains with n=2 (5 RF pulses total) were foundto be optimal, as improvements in the shape of the profile with higher nwere offset by increased T2 decay during the pulse. The hyperecho pulsetrain is not constrained to a beginning with a 90° pulse because thisbeginning with a 90° pulse may unnecessarily reduce the degrees offreedom for the optimization.

If the final RF pulse is set to −α₁ (with phase −φ₁), then staticmagnetization will be left inverted. If it is set to 180°−α₁ (with phase−φ₁), then static magnetization will be returned to the +Z axis. Eitherof these can be used for VS-ASL because each of the above two final RFpulses results in the same difference in Mz between static and flowingspins. The inverted case naturally results in at least partialsuppression of the static tissue signal to reduce noise in the timeseries and the dynamic range of the signal, which can be useful for highdynamic range imaging methods such as volume acquisitions.

FIG. 4 shows an optimized hyperecho pulse train as one example.Parameters of this pulse are: α={58.2, −94.1, 180, 94.1,−58.2}°,φ={86.0°, −113.6, 0,113.6, −86.0}°, gradient durations are {0.79, 2.37,0.79, 2.34}ms, using trapezoidal gradients of 3 G/cm amplitude and rampsslewed at 14 G/cm/ms. Note that the phase and amlitude of the RF pulseare nonlinear functions of time. FIG. 5 shows a calculated velocityprofile for this pulse for the non-inverted pulse train where the sincprofile of a spin echo VS pulse is shown for comparison., FIG. 5 alsoillustrates the improved sharpness of the velocity cutoff, as well asthe flatter profile near zero velocity. FIG. 6 shows an example VS-ASLimage acquired in 200 s on a Varian 3 T scanner using a single shot EPIreadout.

The velocity profile of the hyperecho based velocity selective pulsetrain is greatly improved relative to a simple spin echo based pulsetrain. The use of B1 insensitive pulses was found to be critical forhyperecho based pulse trains, as they were found to be exquisitelysensitive to both B1 and resonance offset when implemented using linearpulses. This is particularly important for implementation at higherfields.

Both B1 insensitive RF pulses and RF pulses insensitive to the resonanceoffset are applications of adiabatic rapid passage techniques in MRIsystems. Some adiabatic rapid passage techniques are described, e.g, byGarwood and DelaBarre in “Advances in Magnetic Resonance—the Return ofthe Frequency Sweep: Designing Adiabatic Pulses for Comtempary NMR,”Journal of Magnetic Resonance, Vol. 153, pages 155-177(2001) and Journalof Magnetic Resonance, Vol. 94, page 511 (1991) by Garwood et al. In theVS-ASL techniques of this application, the phase, frequency, amplitude,or a combination of these parameters of the RF pulses may be varied inan adiabatic manner to allow the spins to follow such an adiabaticvariation. Such adiabatic rotations are rapid relative to the relationstimes T1 and T2 of the spins. Hence, the B1 insensitive RF pulses may bedesigned to adiabatically change its RF frequency with time, or changeits phase in a nonlinear manner with respect to time, to allow forefficient MRI acquisitions with a high degree of tolerance to avariation in the B1 field, e.g., its amplitude above a certain thresholdamplitude, or its spatial inhomogeneity. Similarly, the RF frequency ofthe RF pulses may be swept in an adiabatic manner in a range thatincludes the Larmor frequency of the spins to allow for tolerance to aresonance offset from the Larmor frequqency in MRI.

The above VS-ASL techniques are amenable to 3-dimensional and multisliceimaging applications. Such techniques may be used for imaging in anumber of settings including, but not limited to stroke and othercerebrovascular diseases, perfusion deficit in brain disorders such asAlzheimers and schizophrenia, functional brain imaging in both clinicalas in neurosurgical planning and epilepsy and in basic researchsettings, myocardial ischemia and other ischemic diseases in otherorgans including lung, kidney and muscle.

Only a few implementations are disclosed. However, it is understood thatvariations and enhancements may be made without departing from thespirit of and are intended to be encompassed by the following claims.

1. A method for magnetic arterial spin labeling in magnetic resonance imaging (MRI), comprising: applying at an MRI system an RF pulse train to selectively tag spins according to velocities of the spins without selection based on locations of the spins; applying at the MRI system a second velocity selective pulse train after the tagging RF pulse train to destroy a signal from spins that are still moving faster than a cut off velocity; and obtaining at the MRI system MRI images of tagged spins at an area of interest to obtain information on perfusion at the area of interest.
 2. The method as in claim 1, wherein the RF pulse train includes a pulse train in a form of 90_(x)−grad−180_(y)−grad−90_(−x) where z is long a direction of a static-magnetic field for the MRI in a xyz coordinate system.
 3. The method as in claim 1, wherein the RF pulse train is a hyperecho pulse train.
 4. The method as in claim 3, wherein the hyperecho pulse train is configured to be insensitive to an RF field B₁ in MRI.
 5. The method as in claim 1, wherein the RF pulse train includes a pulse train in a form of (α_(i)−grad_(i))_(n)−180−(−α_(n+1−i)−grad_(n+1−i))_(n) where z is long a direction of a static-magnetic field for the MRI in a xyz coordinate system.
 6. The method as in claim 1, further comprising obtaining at the MRI system a 3-dimensional MRI image based on the tagging according to velocities of the spins without selection based on locations of the spins.
 7. The method as in claim 1, further comprising obtaining at the MRI system multislice MRI images based on the tagging according to velocities of the spins without selection based on locations of the spins.
 8. The method as in claim 1, wherein the RF pulse train is configured to be insensitive to a resonance offset.
 9. The method as in claim 1, further comprising applying at the MRI system a second velocity selective pulse train which is added between the tagging pulse train and the image acquisition to improve the quantitation of perfusion.
 10. The method as in claim 1, wherein MRI images are acquired with a velocity selective pulse train to improve the quantitation of perfusion.
 11. The method as in claim 10, wherein the velocity selective pulse train for image acquisition includes bipolar gradient pulses.
 12. A method for magnetic arterial spin labeling in magnetic resonance imaging (MRI), comprising: applying at a MRI a velocity-selective tagging RF pulse train to selectively tag spins according to velocities of arterial spins flowing to an area of interest without selection based on locations of the arterial spins; obtaining at the MRI a first MRI image of tagged arterial spins at the area of interest; obtaining a second MRI image of the area of interest without the velocity-selective tagging RF pulse; obtaining at the MRI system a difference between the first and the second MRI images to obtain information on perfusion at the area of interest; and applying at the MRI system a second velocity selective pulse train between the tagging RF pulse train and the acquisition of the first MRI image to improve the quantitation of perfusion.
 13. The method as in claim 12, wherein the RF pulse train includes a pulse train in a form of 90_(x)−grad−180_(y)−grad−90_(−x) where z is long a direction of a static magnetic field for the MRI in a xyz coordinate system.
 14. The method as in claim 12, wherein the RF pulse train is a hyperecho pulse train.
 15. The method as in claim 14, wherein the hyperecho pulse train is configured to be insensitive to an RF field B₁ in MRI.
 16. The method as in claim 12, wherein the RF pulse train includes a pulse train in a form of (α_(i)−grad_(i))_(n)−180−(−α_(n+1−i)−grad_(n+1−i))_(n) where z is long a direction of a static magnetic field for the MRI in a xyz coordinate system.
 17. The method as in claim 12, further comprising obtaining at the MRI system a 3-dimensional MRI image based on the tagging according to velocities of the spins without selection based on locations of the spins.
 18. The method as in claim 12, further comprising obtaining at the MRI system multislice MRI images based on the tagging according to velocities of the spins without selection based on locations of the spins.
 19. The method as in claim 12, wherein MRI images are acquired with a velocity selective pulse train to improve the quantitation of perfusion.
 20. The method as in claim 19, wherein the velocity selective RF pulse train for image acquisition includes bipolar gradient pulses.
 21. The method as in claim 12, wherein the RF pulse train is configured to be insensitive to a resonance offset. 